Selenium (Se) is an essential trace element that plays a critical role in many biological processes, such as reproduction, thyroid hormone metabolism, DNA synthesis and protection from oxidative damage and infection. Selenium is incorporated at the catalytic site of various selenium dependent enzymes such as glutathione peroxidase (GPx), thioredoxin reductases and one methionine-sulfoxidereductase. These selenoenzymes contribute to regulation of metabolic activity, immune function, antioxidant defense, intracellular redox regulation and mitochondrial function.
In addition, results in the literature indicate that different chemical forms of selenium have different bioactivities. For example, a selenozolidine was more effective at reducing the number of lung tumors than selenomethionine. (Poerschke et al, J Biochem Molecular Toxicology 2012 26:344). Barger et al. showed that mice fed different sources of selenium, for example, selenium methionine, sodium selenite and selenized yeast, had differential effects on gene expression and on specific functional pathways of mitochondrial structure and function. (Barger et al, Genes and Nutrition 2012 7:155). Selenized yeast contains many selenium and sulfur compounds but not all of the selenium compounds in selenized yeast impact biological processes. In addition, a mixture of selenium and sulfur compounds in selenized yeast have been shown to be inhibitory to each other, to negatively impact biological processes, or be toxic to cells.
Noninsulin-Dependent (Type II) Diabetes Mellitus (DM) is a disease characterized by insulin resistance in skeletal muscle, liver and fat, combined with defects in insulin secretion due to pancreatic β-cell function. Insulin resistance is a central feature of Type II diabetes. In liver, members of the Forkhead Box Class O (FOXO) gene transcription factor family become activated in their unphosphorylated state and they reside in the cell nucleus. In the nucleus, FOXO transcription factors bind to the promoter region of genes, such as Glucose 6-Phosphatase (G6PC). Together with other transcription factors, such as PGC-1α, increased transcription of G6PC occurs, thereby increasing the rate of glucose production. Glucose 6-phosphatase also catalyzes the last step in gluconeogenesis and glycogenolysis causing the release of glucose from the liver. Therefore, G6PC is important in the control of glucose homeostasis, particularly in diabetic subjects.
The apparent difference in bioactivity and availability of distinct chemical forms of selenium requires identification of compounds containing selenium that positively impact biological processes. In particular, there is a need to characterize the effects of selenium in insulin replacement, enhanced insulin activity, inhibition of glucose production, or modulation of glucose metabolism in various biological pathways. Further, there is a need to determine the effect of selenium compounds and their efficacy as insulin replacement therapies for individuals suffering from Type I or Type II diabetes.